Identification of an alternative 5′‐untranslated exon and new polymorphisms of angiotensin‐converting enzyme 2 gene: Lack of association with SARS in the Vietnamese population

Abstract

We analyzed genetic variations of angiotensin-converting enzyme 2 (ACE2), considering that it might influence patients' susceptibility to severe acute respiratory syndrome-associated coronavirus (SARS-CoV) or development of SARS as a functional receptor. By cloning of the full-length cDNA of the ACE2 gene in the lung, where replication occurs on SARS-CoV, it was shown that there are different splicing sites. All exons including the new alternative exon, exon-intron boundaries, and the corresponding 5'-flanking region of the gene were investigated and 19 single nucleotide polymorphisms (SNPs) were found. Out of these, 13 SNPs including one non-synonymous substitution and three 3'-UTR polymorphisms were newly identified. A case control study involving 44 SARS cases, 16 anti-SARS-CoV antibody-positive contacts, 87 antibody-negative contacts, and 50 non-contacts in Vietnam, failed to obtain any evidence that the ACE2 gene polymorphisms are involved in the disease process in the population. Nevertheless, identification of new 5'-untranslated exon and new SNPs is considered helpful in investigating regulation of ACE2 gene expression in the future.

The transcription factor HNF1α induces expression of angiotensin-converting enzyme 2 (ACE2) in pancreatic islets from evolutionarily conserved promoter motifs

“…The transcription initiation sites indicated in Fig. 1E are those reported by Itoyama et al [13], as they used a method for cloning of cDNA from only full-length ACE2 mRNA with a 5′ cap. The mouse ACE2 promoter is likewise bipartite with the majority of ACE2 mRNA molecules in the pancreas originating from the proximal promoter region.…”

“…The mouse ACE2 promoter is likewise bipartite with the promoter regions separated by short interspersed elements, whereas they are contiguous in the cow, horse, dog and rabbit genomes. For both humans and mice, there exist ACE2 mRNAs with transcriptional initiation in the proximal promoter region and mRNAs with initiation in the distal promoter region [13, 14]. These are termed distal promoter transcripts (DPT) and proximal promoter transcripts (PPT), and they encode the same ACE2 protein.…”

Association study of ACE2 (angiotensin I-converting enzyme 2) gene polymorphisms with coronary heart disease and myocardial infarction in a Chinese Han population

“…The ACE2 gene is located on the X chromosome (Xp22) with 19 exons plus a newly identified 5 -untranslated exon [6,7,12]. It has been mapped to a QTL (quantitative trait locus) associated with hypertension in three rat models of high BP (blood pressure) [10].…”

Angiotensin converting enzyme 2 is primarily epithelial and is developmentally regulated in the mouse lung

“…In humans a 19th exon of ACE2 (exon 1a, National Institutes of Health GenBank accession No. AB193259) has recently been identified as well [Itoyama et al, 2005]. The murine and human ACE2 genes are both located on chromosome X and share 83% nucleotide identity [Komatsu et al, 2002].…”